INCREASED CALCIUM CURRENT IN CAROTID-BODY GLOMUS CELLS FOLLOWING IN-VIVO ACCLIMATIZATION TO CHRONIC HYPOXIA

1. Rat pups were gestated and born in normoxia (inspired O-2 pressure 149 mmHg) or chronic hypoxia (inspired O-2 pressure 80 mmHg) to test w hether chronic hypoxia alters carotid body glomus cell calcium current s. Carotid bodies were removed from 5- to 8-day-old pups under halotha ne anesthesia, at which time blood hematocrits averaged 52 +/- 1% (mea n +/- SE) in the chronically hypoxic pups and 36 +/- 1% in the normoxi c pups (P < 0.05). Glomus cells were then enzymatically isolated from the carotid bodies, and calcium currents were recorded with whole cell patch clamp. 2. Compared with normoxic glomus cells (n = 29), chronic ally hypoxic glomus cells (n = 32) superfused with 10 mM CaCl2 had lar ger peak calcium current (146 +/- 16 pA vs. 49 +/- 7 pA, P < 0.05), la rger peak calcium current density (12.0 +/- 1.1 pA/pF vs. 7.3 +/- 1.0 pA/pF, P < 0.05), and larger membrane capacitance (12.1 +/- 0.9 pF vs. 7.5 +/- 0.6 pF, P < 0.05). 3. Threshold for calcium current activatio n was approximately -40 mV. Currents showed little inactivation during 45-ms test pulses and were half-inactivated by a steady holding volta ge of -11 +/- 2 mV (n = 15). Currents were reduced 43 +/- 13% by 50 mu M nifedipine (n = 6, P < 0.05), and were augmented with barium as the charge carrier. These properties suggest that glomus cell calcium cur rent is carried in part through L-type channels, and that it is relati vely resistant to steady-state inactivation. 4. Augmented calcium infl ux through voltage-gated channels in glomus cells from chronically hyp oxic neonatal rats may increase carotid body excitability through incr eased stimulus-secretion coupling. Overall, acclimatization to chronic hypoxia is known to depress acute hypoxic ventilatory reflex response s in neonates. The observations reported hen suggest that inhibition o f ventilatory reflexes by chronic hypoxia in neonates occurs centrally rather than peripherally.